Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol

Endocannabinoids acting on CB₁ cannabinoid receptors are involved in short- and long-term depression of synaptic transmission. The aim of the present study was to determine which endocannabinoid, anandamide or 2-arachidonoylglycerol (2-AG), is involved in depolarization-induced suppression of inhibition (DSI) in the cerebellar cortex, which is the most widely studied form of short-term depression. Depolarization of Purkinje cells in the mouse cerebellum led to an increase in intracellular calcium concentration and to suppression of the inhibitory input to these neurons (i.e. DSI occurred). Orlistat and RHC80267, two blockers of sn -1-diacylglycerol lipase, the enzyme catalysing 2-AG formation, abolished DSI by acting downstream of calcium influx. In contrast, DSI occurred also in the presence of a phospholipase C inhibitor. Intact operation of the calcium-dependent messengers calmodulin and Ca²⁺–calmodulin-dependent protein kinase II were necessary for DSI. DSI was potentiated by an inhibitor of the main 2-AG-degrading enzyme, monoacylglycerol lipase. Interference with the anandamide metabolizing enzyme, fatty acid amide hydrolase, did not modify DSI. Thus, three kinds of observations identified 2-AG as the endocannabinoid involved in DSI in the mouse cerebellum: DSI was abolished by diacylglycerol lipase inhibitors; DSI was potentiated by a monoglyceride lipase inhibitor; and DSI was not changed by an inhibitor of fatty acid amide hydrolase. Further experiments indicated that 2-AG is the endocannabinoid mediating short-term retrograde signalling also at other synapses: orlistat abolished DSI in the rat cerebellum, DSI in the mouse substantia nigra pars reticulata and depolarization-induced suppression of excitation in the mouse cerebellum.     

Detection of enteric campylobacteriosis in children.

Campylobacter fetus subsp. jejuni was recovered as the sole bacterial pathogen from 31% of 0- to 8-month-old children with acute gastroenteritis and from 5% of asymptomatic children (P less than 0.05). In children 8 to 24 months old, the respective recovery rates were 38 and 40%. With the exception of one case of simultaneous bacteremia, the clinical course of the symptomatic infection was benign and rarely lasted more than a week. The isolates were sensitive to most commonly used antibiotics. Several isolates shared antigenic determinants with C. fetus subsp. intestinalis. A bacteriophage specific for C. fetus subsp. jejuni lysed 73% of the strains. Several phage-resistant isolates carried a phage that lysed the stock strain of C. fetus subsp. jejuni (NADC 917).     

Hospital financial performance under the prospective payment system by type of admission: psychiatric versus medical/surgical.

We performed detailed simulations of DRG-based payments to general hospitals for treatment of nonexempt psychiatric and medical/surgical patients under Medicare's prospective payment system (PPS). We then compared these results to calculated costs for the same patients. Hospitals without specialized psychiatric units tend to fare better financially on their psychiatric than on their medical/surgical caseloads, although the levels of gain for these two types of patients are correlated. Hospitals with nonexempt psychiatric units generally have similar rates of gain on psychiatric and medical/surgical patients. Comparing psychiatric treatment in "scatter-bed" sites with that provided in nonexempt units, the higher rate of gain under PPS for treatment in scatter beds results largely from shorter lengths of stay. We discuss hospital behavior and the relationships between treatment of psychiatric illness under DRG-based payment and its treatment in exempt psychiatric units, which are excluded from DRG-based payment.     

Effect of Percoll wash on sperm motion parameters and subsequent fertility in intrauterine insemination cycles

Purpose This study examined sperm motion parameters as measured by computerized automated semen analysis before and after a Percoll wash and determined if differences in any parameter were correlated with fertility subsequent to intrauterine insemination (IUI).Results Total motile sperm decreased following the washing procedure from 79.0 ± 9.0 to 37.2 ± 7.6 million sperm. Motility increased from a mean of 43.4% to 61.7% (P<0.001). Other motility parameters also changed significantly (P<0.001) as follows: curvilinear velocity (VCL), 43.4 to 61.7 m/s; straight-line velocity (VSL), 21.3 to 26.7 m/s; linearity 53.1 to 45.2%; lateral head displacement (ALH), 2.97 to 3.94 m. Similar changes occurred following a swim-up preparation, although changes in mean motility, VCL, and ALH were significantly greater when compared to Percoll. The postwash changes were not accounted for merely by time lapse in preparation since reanalyzed untreated controls did not show the same changes in motion parameters. Prewash linearity in those specimens which resulted in pregnancies was greater than in those which did not (P=0.28). No other significant differences in pre-or post-Percoll washed sperm motion parameters were found between pregnant vs nonfertile cycles.Conclusion Following Percoll wash all CASA-generated motility parameters were significantly altered, but there was little association between these parameters and pregnancy achieved in IUI cycles.Presented at the 50th Annual Meeting of the American Fertility Society, San Antonio, Texas, November 5–10, 1994.     

Risk and risk factors for epilepsy in shunt-treated children with hydrocephalus

ObjectEpilepsy is a major comorbidity in children with hydrocephalus (HC) and has a serious impact on their developmental outcomes. There are variable influencing factors, thus the individual risk for developing epilepsy remains unclear. Our aim was to analyse risk factors for developing epilepsy in children with shunted HC.MethodsA retrospective, single-centre analysis of 361 patients with the diagnosis of HC was performed. Age at HC diagnosis, shunt treatment, development of epilepsy, epilepsy course, and the aetiology of HC were considered. The influence of shunt therapy, including its revisions and complications, on the development of epilepsy was investigated.ResultsOne-hundred forty-three patients with HC (n = 361) had a diagnosis of epilepsy (39.6%). The median age at the first manifestation of epilepsy was 300 days (range:1–6791; Q1:30, Q3: 1493). The probability of developing epilepsy after HC decreases with increasing age. The most significant influence on the development of epilepsy is that of the HC itself and its underlying aetiology (HR 5.9; 95%-CI [3–10.5]; p < 0.001). Among those, brain haemorrhage is associated with the highest risk for epilepsy (HR 7.9; 95%-CI [4.2–14.7]; p < 0.01), while shunt insertion has a lower influence (HR 1.5; 95%-CI [0.99; 2.38]; p = 0.06). The probability of epilepsy increases stepwise per shunt revision (HR 2.0; p = 0.03 after 3 or more revisions). Five hundred days after the development of HC, 20% of the children had a diagnosis of epilepsy. Shunt implantation at a younger age has no significant influence on the development of epilepsy nor does sex.ConclusionChildren with HC are at high risk for developing epilepsy. The development of epilepsy is correlated mainly with HC's underlying aetiology. The highest risk factor for the development of epilepsy seems to be brain haemorrhage. The age at shunt implantation appears to be unrelated to the development of epilepsy, while structural brain damage at a young age, shunt revisions and complications are independent risk factors. The onset of epilepsy is most likely to take place within the first 500 days after the diagnosis of HC.     

Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis.

von Recklinghausen neurofibromatosis (NF1) is a common hereditary disorder characterized by neural crest-derived tumors, particularly benign neurofibromas whose malignant transformation to neurofibrosarcomas can be fatal. The NF1 gene has been mapped to a small region of chromosome 17q, but neither the nature of the primary defect nor the mechanisms involved in tumor progression are understood. We have tested whether NF1 might be caused by the inactivation of a tumor suppressor gene on 17q, analogous to that on chromosome 22 in NF2, by searching for deletions of chromosome 17 in NF1-derived tumor specimens. Both neurofibrosarcomas from patients with "atypical" NF and 5 of 6 neurofibrosarcomas from NF1 patients displayed loss of alleles for polymorphic DNA markers on chromosome 17. However, the common region of deletion was on 17p and did not include the NF1 region of 17q. Since no loss of markers on chromosome 17 was observed in any of 30 benign tumors from NF1 patients, the 17p deletions seen in neurofibrosarcomas are probably associated with tumor progression and/or malignancy. This region contains a candidate gene for tumor progression, p53, which has recently been implicated in the progression of a broad array of human cancers. In a preliminary search for p53 aberrations by direct sequencing of polymerase chain reaction-amplified DNA from 7 neurofibrosarcomas, 2 tumors that contained point mutations in exon 4 of the p53 gene were found, suggesting a role for this gene in at least some neurofibrosarcomas. Thus the formation of malignant neurofibrosarcomas may result from several independent genetic events including mutation of the NF1 gene, whose mechanism of tumorigenesis remains uncertain, and subsequent loss of a "tumor suppressor" gene on 17p, most likely p53.     

Intravenous verapamil therapy in imminent myocardial infarction

We studied 16 patients with small myocardial infarction who had further episodes of chest pain with ST-segment elevation, a sign of transmural myocardial ischemia and imminent infarction extension. Coronary angiography in 14 showed a critical lesion in 13. Intravenous verapamil abolished chest pain and ST-segment elevation. It caused a fall in right atrial and left ventricular end-diastolic pressures (LVEDP) and cardiac output, reflex systemic vasoconstriction, and a rise in systemic vascular resistance. There was no reflex tachycardia. Volume expansion raised LVEDP and restored a normal cardiac output. Accelerated junctional rhythm with isorhythmic A-V dissociation occurred in 5 patients. Two patients sustained a transmural infarction, 10 underwent coronary artery bypass grafting, and 4 are symptom-free with oral treatment. Intravenous treatment was an effective method of treating acute episodes of transmural myocardial ischemia and preventing their recurrence in patients with critical coronary artery narrowing. Continuous verapamil infusion stabilized the patients' condition and enabled smooth coronary angiography and induction of anesthesia for surgery.     

Intracranial pressure monitoring in posterior fossa lesions—systematic review and meta-analysis

Neurosurgical Review - Elevated intracranial pressure (ICP) with reduced cerebral perfusion pressure is a well-known cause of secondary brain injury. Previously, there have been some reports...